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Protective effect of nicorandil against myocardial ischemia/reperfusion injury mediated via IL33/ST2 signaling pathway

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Abstract

Myocardial ischemia–reperfusion injury (MI/RI), a complication of myocardial injury, is associated with high rates of mortality and disability. We aimed to explore the effect of nicorandil™ against MI/RI and investigated the underlying molecular mechanisms. In this in vitro study, hypoxia/reoxygenation (H/R) processing of H9c2 cells significantly suppressed the expressions of IL33 and ST2, reduced cell viability, increased production of reactive oxygen species, downregulated protein expression of Bcl-2, upregulated protein expressions of Bax, cleaved caspase3, and cleaved PARP, increased intracellular calcium overload, and induced cell apoptosis. Nicorandil processing reduced H/R-induced H9c2 cell damage. Nicorandil processing ameliorated the H/R-induced inhibition of the IL33 and ST2 expression in H9c2 cells. 5-Hydroxydecanoate blocked the effects of nicorandil on H9c2 cell viability, ROS production, and apoptosis and inhibited both IL33 and ST2. Similarly, the protective effect of nicorandil was restrained after inhibition of the IL33/ST2 pathway. Our findings suggest that the protective effect of nicorandil against H/R-induced H9c2 cell apoptosis was mediated through IL33/ST2 signaling pathway.

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The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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Authors and Affiliations

  1. Department of Cardiology, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of China

    Yi Zheng, Xueyin Li, Fan Zhang, Bo Zhao, Wanting Du, Da Sun & Guangping Li

  2. Department of Cardiology, Tianjin Institute of Cardiology, the Second Hospital of Tianjin Med University, Tianjin, 300211, People’s Republic of China

    Guangping Li

Authors
  1. Yi Zheng
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  2. Xueyin Li
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  3. Fan Zhang
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  4. Bo Zhao
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  5. Wanting Du
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  6. Da Sun
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  7. Guangping Li
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Contributions

Y Z, XY L and FZ performed the experiments; B Z, WTD, and D S performed data analysis; Y Z, XYL and GP L designed the study; Y Z and GP L wrote the manuscript. All authors read and approved the final manuscript.

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Correspondence to Guangping Li.

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Zheng, Y., Li, X., Zhang, F. et al. Protective effect of nicorandil against myocardial ischemia/reperfusion injury mediated via IL33/ST2 signaling pathway. Mol Cell Biochem 477, 1921–1929 (2022). https://doi.org/10.1007/s11010-022-04418-z

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  • DOI: https://doi.org/10.1007/s11010-022-04418-z

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